14-92923058-A-T

Variant names:

• chr14-92923058-A-T
• rs7159323
• ENST00000903321.1:c.-189+46A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000903321.1(CHGA):​c.-189+46A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHGA ENST00000903321.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 12 publications found

Genes affected

CHGA (HGNC:1929): (chromogranin A) The protein encoded by this gene is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. It is found in secretory vesicles of neurons and endocrine cells. This gene product is a precursor to three biologically active peptides; vasostatin, pancreastatin, and parastatin. These peptides act as autocrine or paracrine negative modulators of the neuroendocrine system. Two other peptides, catestatin and chromofungin, have antimicrobial activity and antifungal activity, respectively. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000903321.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGA	NM_001275.4	MANE Select	c.-302A>T		upstream_gene	N/A	NP_001266.1	P10645
	CHGA	NM_001301690.2		c.-302A>T		upstream_gene	N/A	NP_001288619.1	G5E968

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGA	ENST00000903321.1		c.-189+46A>T		intron	N/A	ENSP00000573380.1
	CHGA	ENST00000216492.10	TSL:1 MANE Select	c.-302A>T		upstream_gene	N/A	ENSP00000216492.5	P10645
	CHGA	ENST00000334654.4	TSL:1	c.-302A>T		upstream_gene	N/A	ENSP00000334023.4	G5E968

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 106542 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 54530

African (AFR) AF: 0.00 AC: 0 AN: 3086

American (AMR) AF: 0.00 AC: 0 AN: 2862

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3910

East Asian (EAS) AF: 0.00 AC: 0 AN: 9270

South Asian (SAS) AF: 0.00 AC: 0 AN: 1026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 874

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 69136

Other (OTH) AF: 0.00 AC: 0 AN: 7140

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.69
PhyloP100		-0.15
PromoterAI		0.46	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7159323; hg19: chr14-93389403;